This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Otitis media (OM) is the most common disease seen in pediatric practice and is recognized as a multifactorial disease with complex and interrelated genetic, environmental and infectious etiologies. We will study the mechanisms by which genetic risk factors (as represented by TNF -308 and IL- 6-174 polymorphisms) render the host OM susceptible and whether environmental factors could modify OM risks in children with genetic predisposition. We will perform a prospective, longitudinal study of 300 infants with and without TNF -308 polymorphism followed from near birth to the first AOM episode up to 1 year of age. Subjects will be screened for the gene polymorphism;equal number of polymorphic and normal infants (matched for gender and race) will be enrolled into the study within the first month of life. The dynamics of nasopharyngeal bacterial colonization in the first 6 mos. of life will be studied;symptomatic URI episodes will be monitored for AOM complication. Information on BF, CSE, and daycare (DC) attendance will be collected prospectively and updated continuously. Incidence of AOM in the first year of life (% of cases with at least one episode in the first year) will be compared between polymorphic and normal children groups;modifying effects of environmental risk factors on bacterial colonization, incidence of viral URI and AOM will be assessed. We will also compare IL- 6-174 polymorphic and normal children. The study is important to public health as it will lay the ground work for the design of innovative approaches to prevent OM.